Leveraging the microbiome to combat antibiotic resistant gynecological infections

The vaginal resistome can be considered a collection of the resistant determinants in the vaginal microbiome. Here we review the vaginal resistome including the microbes and resistant genes harbored in common gynecological infections, vaginal microbes that participate in horizontal gene transfer, host factors that contribute to the resistome, and common therapies. Finally, we provide perspective on technologies that can be leveraged to study the vaginal resistome and remaining challenges

Danger- and pathogen-associated molecular patterns recognition by pattern-recognition receptors and ion channels of the transient receptor potential family triggers the inflammasome activation in immune cells and sensory neurons.

An increasing number of studies show that the activation of the innate immune system and inflammatory mechanisms play an important role in the pathogenesis of numerous diseases. The innate immune system is present in almost all multicellular organisms and its activation occurs in response to pathogens or tissue injury via pattern-recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). Intracellular pathways, linking immune and inflammatory response to ion channel expression and function, have been recently identified. Among ion channels, the transient receptor potential (TRP) channels are a major family of non-selective cation-permeable channels that function as polymodal cellular sensors involved in many physiological and pathological processes.In this review, we summarize current knowledge of interactions between immune cells and PRRs and ion channels of TRP families with PAMPs and DAMPs to provide new insights into the pathogenesis of inflammatory diseases. TRP channels have been found to interfere with innate immunity via both nuclear factor-kB and procaspase-1 activation to generate the mature caspase-1 that cleaves pro-interleukin-1ß cytokine into the mature interleukin-1ß.Sensory neurons are also adapted to recognize dangers by virtue of their sensitivity to intense mechanical, thermal and irritant chemical stimuli. As immune cells, they possess many of the same molecular recognition pathways for danger. Thus, they express PRRs including Toll-like receptors 3, 4, 7, and 9, and stimulation by Toll-like receptor ligands leads to induction of inward currents and sensitization in TRPs. In addition, the expression of inflammasomes in neurons and the involvement of TRPs in central nervous system diseases strongly support a role of TRPs in inflammasome-mediated neurodegenerative pathologies. This field is still at its beginning and further studies may be required.Overall, these studies highlight the therapeutic potential of targeting the inflammasomes in proinflammatory, autoinflammatory and metabolic disorders associated with undesirable activation of the inflammasome by using specific TRP antagonists, anti-human TRP monoclonal antibody or different molecules able to abrogate the TRP channel-mediated inflammatory signals

Critical Language and Discourse Awareness in Management Education

Communication and, through it, language have become key elements of business and organizational life. How organizations interact within their walls and with the outside world fundamentally affects business processes, creating organizational culture, shaping public perceptions, and influencing consumer choices. This essay calls for a greater acknowledgment of language and communication and suggests that management educators may want to review how they are incorporated in management education curricula. Expanding on the skill-based approach typically adopted in business school classes, the essay points to the utility of exposing business students to the dual function of language as a means of doing work and as a social action that constitutes social reality. Drawing on examples from scholarship in linguistics and discourse analysis, the essay demonstrates that the ability to notice, identify, and reflect on linguistic and discourse practices is a crucial managerial skill. Nurturing such analytical and thinking skills enables people to become not only better communicators but also critical thinkers able to understand and challenge when social control, power, or injustice is enacted in organizations

Key components of learning ecologies: a Delphi assessment

This is the accepted version of the following article: González‐Sanmamed, M. , Muñoz‐Carril, P. and Santos‐Caamaño, F. (2019), Key components of learning ecologies: A Delphi assessment. Br J Educ Technol, 50: 1639-1655, which has been published in final form at https://doi.org/10.1111/bjet.12805. This article may be used for non-commercial purposes in accordance with the Wiley Self-Archiving Policy (http://www.wileyauthors.com/self-archiving)The educational landscape has changed in recent years, requiring reflection about new pedagogical methods and theories. There are three important perspectives as drivers of pedagogical reflection: lifelong and life‐wide learning, the idea of learning as a social construct in which internal elements and changing external factors converge, and the recognition of technology as a resource that can promote ubiquitous and expanded learning. Learning ecology has been proposed as a conceptual and empirical framework, but its still emergent nature along with its multidimensionality and complexity require further exploration. The Delphi study we present as part of a broader research project aims to identify the components of learning ecologies. Three panel rounds with international experts were carried out, after which two important dimensions emerged in the structure of learning ecologies. The first is related to intrinsic “learning dispositions,” which is made up of three categories: the subject's ideas about learning, their motivations and expectations. The second dimension, called “learning processes,” comprises four components: relationships, resources, actions and context. The identification of the components of learning ecologies and their influence on formal, non‐formal and informal training processes will provide guidance for educational policies and help to better organize training programmesWe thank the Spanish Ministry of Economy and Competitiveness for their support of our study under a research project entitled “How the best University Teachers Learn: Impact on Learning Ecologies on Quality of Teaching” (ECO4LEARN‐HE) (Reference: EDU2015‐67907‐R)S

Altered ontogeny and transcriptomic signatures of tissue-resident pulmonary interstitial macrophages ameliorate allergic airway hyperresponsiveness

IntroductionEnvironmental exposures and experimental manipulations can alter the ontogenetic composition of tissue-resident macrophages. However, the impact of these alterations on subsequent immune responses, particularly in allergic airway diseases, remains poorly understood. This study aims to elucidate the significance of modified macrophage ontogeny resulting from environmental exposures on allergic airway responses to house dust mite (HDM) allergen.MethodsWe utilized embryonic lineage labeling to delineate the ontogenetic profile of tissue-resident macrophages at baseline and following the resolution of repeated lipopolysaccharide (LPS)-induced lung injury. We investigated differences in house dust mite (HDM)-induced allergy to assess the influence of macrophage ontogeny on allergic airway responses. Additionally, we employed single-cell RNA sequencing (scRNAseq) and immunofluorescent staining to characterize the pulmonary macrophage composition, associated pathways, and tissue localization.ResultsOur findings demonstrate that the ontogeny of homeostatic alveolar and interstitial macrophages is altered after the resolution from repeated LPS-induced lung injury, leading to the replacement of embryonic-derived by bone marrow-derived macrophages. This shift in macrophage ontogeny is associated with reduced HDM-induced allergic airway responses. Through scRNAseq and immunofluorescent staining, we identified a distinct subset of resident-derived interstitial macrophages expressing genes associated with allergic airway diseases, localized adjacent to terminal bronchi, and diminished by prior LPS exposure.DiscussionThese results suggest a pivotal role for pulmonary macrophage ontogeny in modulating allergic airway responses. Moreover, our findings highlight the implications of prior environmental exposures in shaping future immune responses and influencing the development of allergies. By elucidating the mechanisms underlying these phenomena, this study provides valuable insights into potential therapeutic targets for allergic airway diseases and avenues for further research into immune modulation and allergic disease prevention

The Rhetorical Analysis of Business Speech: Unresolved Questions

Serious attention to the rhetorical analysis and criticism of the public discourse of business leaders can offer important insights about influential participants in political and social decision-making processes, contributing to the development of a coherent body of scholarship that addresses communication at the intersection of business, rhetoric, and society. © 2010 by the Association for Business Communicatio

A PMMA bone cement composite that functions as a drug-refillable depot for localized, multi-window chemotherapeutic treatment of bone cancer

ABSTRACTStandard chemotherapy for primary and secondary bone tumors typically involves systemic administration of chemotherapeutic drugs, such as doxorubicin (DOX). However, non-targeted delivery increases dose requirements, and results in off-target toxicity and suboptimal chemotherapeutic efficacy. When chemotherapy is ineffective, substantial resection of tissue and/or total amputation become necessary – a debilitating outcome for any patient. In this work, we developed a proof-of-concept, non-biodegradable, mechanically robust, and refillable composite system for chemotherapeutic (i.e. DOX) delivery comprised of poly(methyl methacrylate) (PMMA) bone cement and insoluble polymeric γ-cyclodextrin (γ-CD) microparticles. The porosity and compressive strength of DOX-filled PMMA composites were characterized. DOX filling capacity, elution kinetics, cytotoxicity against primary osteosarcoma and lung cancer cells, and refilling capacity of composites were evaluated. PMMA composites containing up to 15wt% γ-CD microparticles provided consistent, therapeutically-relevant release of DOX with ~100% of the initial DOX released after 100 days. Over the same period, only ~6% of DOX was liberated from PMMA with free DOX. Following prolonged curing, PMMA composites with up to 15wt% γ-CD surpassed compressive strength requirements outlined by international standards for acrylic bone cements. Compared to DOX-filled PMMA, DOX-filled PMMA/γ-CD composites provided long-term release with decreased burst effect, correlating to long-term cytotoxicity against cancer cells. Refillable properties demonstrated by the PMMA composite system may find utility for treating local recurrences, limiting chemoresistance, and altering drug combinations to provide customized treatment regimens. Overall, findings suggest that PMMA composites have the potential to serve as a platform for the delivery of combinatorial chemotherapeutics to treat bone tumors.</jats:p